The present invention generally relates to an imaging method for determining a physical or chemical condition of tissue in human or animal bodies using ultrasound, where at least one ultrasonic pulse in the diagnostic frequency and power range is directed into the tissue, and the ultrasonic echo pulse reflected by the tissue is received and processed in ultrasonographic image processing means.
The invention further generally relates to an imaging system for determining a physical or chemical condition of tissue in human or animal bodies using ultrasound, having ultrasound-generating means for generating at least one ultrasonic pulse in the diagnostic frequency and power range, ultrasound application means for applying the ultrasonic pulse into the tissue, ultrasound receiving means for receiving the ultrasonic echo pulse reflected in the tissue and ultrasonographic image processing means for processing the ultrasonic echo pulse.
An imaging method of the before-mentioned kind, also known as ultrasonic echo pulse method, and an imaging system of the before-mentioned kind are generally known.
In imaging methods of this kind an electric pulse is converted to an ultrasonic pulse for example by means of a piezoelectric ultrasonic transducer. The electronic pulse is then injected into the tissue under examination. As the ultrasonic pulse enters the tissue, part of it is reflected at the boundary surfaces of the tissue, while part of it penetrates deeper into ion the tissue. Consequently, this method permits several tissue layers, lying one behind the other, to be localized and the condition of those tissue layers to be determined.
Physical condition in the meaning of the present invention is meant to describe, for example, geometrical parameters, such as the extension in space, the position in space, the thickness of the tissue, as well as other physical variables, such as the density of the tissue under examination as a function of the locus. The method is, however, also simply used to describe the visual display of tissue in an image-display unit. The term chemical condition is used, for example, to describe the composition of the tissue.
The ultrasonic echo pulse method allows tissues of organs to be visually displayed and information regarding the tissue to be acquired, it being possible, for example, to determine a pathological condition of the tissue by evaluation of the ultrasonographic image. In order to generate a two-dimensional sectional image a continues sequence of ultrasonic pulses is injected into the tissue through a scanning process which may be of an electronic or mechanical kind.
The advantages of the ultrasonic echo pulse method over the x-ray imaging method lie mainly in the fact that it protects the tissue and can be realized at low cost. Another advantage of the ultrasonic echo pulse method is the relatively great depth of penetration of the ultrasonic pulses into the tissue.
A disadvantage of the ultrasonic echo pulse method lies, however, in the comparatively low axial resolution of the ultrasonographic image. The term axial resolution as used in this connection means the resolution along the axis of irradiation. The resolution along the axis of irradiation is dependent from the frequency and spread of the injected ultrasonic pulse.
At present, standard frequencies in the range of between 5 to 10 MHz are used for the abdominal region. For special tissue structures near the surface, frequencies of up to 50 MHz are already used today. Although such high frequencies achieve improved axial resolution, the attenuation coefficient of the tissue likewise increases linearly with the frequency so that in the case of very high frequencies, which in principle would allow improved resolution, the depth of penetration of the ultrasound into the tissue is heavily limited due to physical reasons so that the advantage of ultrasound, namely that depth information can be obtained about the tissue in a tissue-sparing way, is lost.
The highest possible axial resolution obtainable with high-frequency ultrasound is at present in a range down to 30 xcexcm.
In WO 97/32182 an optical imaging method is described which is known as xe2x80x9coptical coherence tomography (OCT)xe2x80x9d. With OCT a light beam is generated and splitted up into a measuring light beam and a reference light beam, the measuring light beam being directed into the tissue to be examined. The relative optical path between the reference light beam and the measuring light beam is adjusted, and the measuring light beam scattered back from the tissue is brought to interference with the reference light beam.
In one embodiment in WO 97/32182 an applicator for applying the measuring light beam into the tissue to be examined is described, which is configured in form of an endoscope, in a tip of which a prism or a silver-coated mirror is disposed so that the measuring light beam is injected into the tissue to be examined perpendicular to the longitudinal axis of the endoscope. An ultrasonic transducer is disposed in the tip of the endoscope which directs ultrasonic waves onto the silver-coated mirror which then are injected from the mirror into the tissue to be examined in opposite direction of the measuring light beam.
Further, from WO 98/55025 an ultrasonographic imaging method is known, where it is proposed to combine the ultrasonographic imaging method with optical coherence tomography. In this document, however, it is not described how to carry out the method of optical coherence tomography in connection with an ultrasonographic imaging method.
It is an object of the present invention to improve an imaging method and an imaging system of the type described above so that improved resolution of the imaging method is achieved in order to obtain more precise information about the tissue without losing the depth information.
According to the present invention, an imaging method for determining a physical or chemical condition of tissue in a human or animal body using ultrasound is provided, comprising the steps of directing at least one ultrasonic pulse in the diagnostic frequency and power range into said tissue along a beam axis, receiving an ultrasonic echo pulse reflected by said tissue, processing said ultrasonic echo pulse in ultrasonographic image processing means, generating at least one light beam and splitting said light beam into at least one measuring light beam and at least one reference light beam, directing said measuring light beam along said beam axis into said tissue, such that said ultrasonic pulse and said measuring light beam are superimposed, adjusting a relative optical path between said reference light beam and said measuring light beam, and bringing said measuring light beam scattered back by said tissue into an interference relationship with said reference light beam and processing the interferometric signal in optical image processing means.
Further, according to the present invention, an imaging system for determining a physical or chemical condition of tissue in a human or animal body using ultrasound is provided, comprising ultrasound-generating means for generating at least one ultrasonic pulse in the diagnostic frequency and poser range, ultrasound application means for applying said ultrasonic pulse into said tissue; ultrasound receiving means for receiving an ultrasonic echo pulse reflected by said tissue, ultrasonographic image processing means for processing said ultrasonic echo pulse, light generating means for generating at least one light beam, beam splitter means for splitting up said light beam into at least one measuring light beam and at least one reference light beam, adjusting means for adjusting a relative optical path between said measuring light beam and said reference light beam, light application means for applying said measuring light beam into said tissue, said light application means and said ultrasound application means being configured such that said ultrasonic pulse and said measuring light beam are superimposed and directed into said tissue along a common beam axis, means for receiving said measuring light beam scattered back by said tissue, means for interferometrically superimposing said back-scattered measuring light beam and said reference light beam, and optical image processing means for processing the interferometric measuring signal.
The invention combines the before-mentioned imaging method using ultrasound with optical coherence tomography, known as such, to an acousto-optical imaging method. For this purpose, the at least one measuring light beam is injected, according to the invention, into the tissue along the same beam axis as the ultrasonic pulse and superimposed therewith. The ultrasound application means and the light application means of the imaging system are correspondingly designed for this purpose for injecting the ultrasound and the light into the tissue along one and the same beam axis.
When the adjustment of the relative optical path between the measuring light beam and the reference light beam is limited to one coherence length, a single image dot is produced. When the optical path is adjusted over a larger area than one coherence length, an initially one-dimensional image is produced in the direction of the injection axis, as the interference signal originates only from the neighborhood of the object spot where identical wavelengths exist between the measuring light beam and the reference light beam. Thus, by adjusting the relative optical path between the measuring light beam and the reference light beam a defined path and/or depth region of the tissue is axially swept in the fashion of a scanning action.
In the context of the invention, the term imaging therefore includes, with respect to the optical path of the measuring method, the generation of an image formed by a one-dimensional sequence of individual image spots. Such an image may, however, also consist of a single image spot. And it is further to be understood that the before-mentioned image processing means is also capable of processing a single measuring signal to produce a single image spot.
The advantages of the method according to the invention, resulting from the combination of the ultrasonic echo pulse method with optical coherence tomography, now lie in the fact that with the aid of optical coherence tomography an axial resolution can be achieved higher than that achievable with the ultrasonic echo pulse method. The resolution achievable with optical coherence tomography is at present in the range of between 5 to 10 xcexcm. The depth of penetration of the measuring light in the tissue is, however, shorter than the depth of penetration of ultrasound. Thus, it is now possible, with the aid of the method according to the invention, to derive from the received optical high-resolution image information about the tissue from tissue regions near the surface, while additional information on the tissue from deeper tissue regions can be derived from the ultrasonographic image. Especially in the region of axial overlapping between the ultrasonographic image and the optical image it is now possible to acquire information about the tissue useful for the characterization of the tissue, which cannot be obtained with either the ultrasonic echo pulse method or optical coherence tomography alone. So, it is possible, for example, to use the optical image for determining the thickness of a tissue layer, and to thereafter derive from the optically determined thickness of the tissue layer and from the time interval between two ultrasonic echo pulses the ultrasonic speed and from the latter information on the elasticity and density of the tissue. Generally, the ultrasonographic image permits an overview image to be obtained of both the surface of the tissue and the deeper regions. This allows to identify suspicious areas which can then be viewed in detail by optical coherence tomography. To say it in other words, optical coherence tomography, combined with the ultrasonic method, provide a sort of a zoom function.
The method may further be used for therapy control. For example, in skin resurfacing coagulation reinforces the optical interference measuring signal so that the therapy can be stopped at the convenient moment.
The method according to the invention and/or the system according to the invention provide an analytical method that allows to differentiate between tissues and to determine pathological changes in the surface structure of tissue. In addition, dynamic processes, such as flowing blood or motions in the tissue, can be visualized by carrying out the method, for example, in the doppler mode or by generating a rapid sequence of separate images. And finally, functional imaging is also rendered possible. Possible fields of application include, for example, the endoscopic quantification of the cartilage tissue in joints or the endoscopic quantification of the epithelial structures of hollow organs, skin structures being examined, etc.
According to a preferred embodiment of the method, the light beam is generated with a spectral bandwidth in a range of between 10 and 200 nm, and/or with a wavelength in the range of between 600 and 2000 nm.
The light-generating means of the system according to the invention comprise for this purpose a light source with a spectral bandwidth in the range of between 10 and 200 nm, and/or with a wavelength in the range of between 600 and 2000 mm.
The axial resolution of the image acquired by optical coherence tomography increases as the spectral bandwidth increases and/or as the coherence length of the light used decreases. The use of a light source with a great spectral bandwidth thus advantageously results in increased resolution of the optical image obtained, and allows, for example, a geometric parameter to be measured very exactly, or the condition of the tissue to be determined very precisely. The light source used may, for example, be a superluminescent diode with a spectral bandwidth of 30 nm and a power of 1.5 mW.
In a further preferred embodiment the ultrasonic pulse is generated in a frequency range between 1 and 200 MHz and preferably with a bandwidth in the range between 5 and 75 MHz. The ultrasound generation means of the image system according to the present invention are suited to generate ultrasonic pulses in the afore-mentioned parameter ranges, accordingly.
According to another preferred embodiment of the method, the relative optical path between the reference light beam and the measuring light beam is adjusted beyond one coherence length of the light.
Adjusting the relative optical path between the reference light beam and the measuring light beam beyond one coherence length produces, advantageously, at least one one-dimensional optical (depth) image in the direction of irradiation, i.e. the tissue is optically scanned in the direction of irradiation by this measure.
According to a further preferred embodiment of the invention, a sequence of ultrasonic pulses which may be continuous is injected into the tissue as ultrasonic beam, the ultrasonic beam and the measuring light beam being superimposed along the common beam axis.
This feature makes it possible to obtain not only one-dimensional but also two-dimensional sectional images, for example by commonly displacing the ultrasonic beam and the measuring light beam, or by injecting them into the tissue by planar application means. It should be noted at this point that the light beam and, thus, the measuring light beam may also consist of a sequence of light pulses or may be emitted continuously.
In this connection, it is preferred according to the method if the common beam axis of the ultrasonic beam and the measuring light beam are displaced in a plane parallel to the tissue surface.
In the case of this system, further means are provided for displacing the beam axis in a plane parallel to the tissue surface.
This feature makes it possible, with little technical input, to scan the tissue laterally by the ultrasound and the light in order to obtain a two-dimensional ultrasonographic trace/optical sectional image. Other preferred ways of producing two-dimensional sectional images consist in the use of ultrasonic and optical systems, such as arrays, that provide planar images.
It is further preferred in the method if the common beam axis of the ultrasonic beam and of the measuring light beam is rotated about a rotary axis transversely to the instantaneous direction of irradiation.
The system is provided for this purpose with corresponding means for rotating the beam axis about a rotary axis transversely to the instantaneous direction of irradiation.
When embodied in this way, the method and the system are especially well suited for generating ultrasonographic traces/optical sectional images of a hollow organ.
According to a further preferred embodiment of the invention, the image obtained optically by processing the back-scattered measuring light beam and the ultrasonographic image obtained by processing the ultrasonic echo pulse are combined one with the other so that the image obtained by optical means is displayed in the near range and the ultrasonographic trace is displayed in the far range.
In the case of the system, the processing means for the ultrasonographic image and the processing means for the optical image are coupled one with the other in such a way that the ultrasonographic image and the optical image can be displayed one superimposed to the other.
The advantage of this arrangement lies in the fact that a very high resolution can be used in the near range and/or that additional information about the tissue is made available by the ultrasonographic image in the far range. In the case of isolated high-frequency ultrasonographic images, the tissue surfaces mostly cannot be differentiated because strong surface echoes at the transition of the tissue interfere with echoes from slightly deeper structures. The combination with optical coherence tomography according to the invention now permits to achieve high-resolution differentiation of the tissue surface.
According to another preferred embodiment of the method, the thickness of the tissue layer near the surface is determined by means of the optical image obtained by processing the back-scattered measuring light beam, the difference in time delay between the ultrasonic echo pulse reflected at a first tissue layer boundary and the ultrasonic echo pulse reflected at a second tissue layer boundary is determined from the ultrasonographic trace, and the sound propagation speed in the tissue layer is determined from the difference in time delay and the thickness.
As has been mentioned before, the combination, according to the invention, of the ultrasonic echo pulse method and optical coherence tomography opens up new possibilities of determining conditions of the tissue being examined, which heretofore could not be determined with either an ultrasonic imaging method or an optical imaging method alone. The feature described before now permits the elasticity and thickness of the tissue being examined to be determined from the sound propagation speed so determined.
The method and/or the device according to the invention find preferred application, as mentioned before, in tissue differentiation and/or the determination of pathological changes in the surface structure of tissue.
According to a preferred embodiment, the ultrasonographic image is used as overview image of the tissue being examined, while the optical image is used for the detailed imaging of selected tissue regions.
The ultrasonographic method, which provides increased depth of penetration, and optical coherence tomography, which provides improved resolution, can be coupled by suitable image processing methods, especially the merging method, so that after the tissue regions, which possibly might be pathologically changed and must, therefore, be examined more closely, have been identified from a xe2x80x9ccoarse overviewxe2x80x9d provided by the ultrasonographic image, details of the tissue being examined can be discerned in the image obtained by optical means.
In addition, as has been mentioned before, the method and the device can be used for therapy control.
According to a further preferred embodiment of the method, fluorescence is additionally induced in the tissue by the measuring light beam or light irradiated into the tissue independently of the light beam, and the fluorescent light is received, and the fluorescent image is displayed in addition to the image obtained by optical means.
In the case of this embodiment of the method according to the invention, the method is combined with what is known as photodynamic diagnosis (PDD). In photodynamic diagnosis, fluorescence is induced, in some instances after administration of a light-sensitive substance into the tissue, which fluorescence can then be used for further differentiation, especially for differentiating between healthy tissue and pathologically changed tissue. For producing surface or sectional images, use can be made in this case either of endogenous autofluorescence or, as has been mentioned before, of xenofluorescence induced by administered drugs. The images so obtained can be used for identifying suspicious areas and also as support for and/or in supplementation of the information gained from the ultrasonographic image and the optical image, for further differentiation.
The method of optical coherence tomography can be combined with photodynamic diagnosis also without the ultrasonographic method, although the combination of ultrasonographic image, optical coherence tomography and photodynamic diagnosis is described as being advantageous in the present specification.
According to a further preferred embodiment of the system, the ultrasound application means and the light application means are both integrated in an applicator designed as endoscope.
An endoscopic applicator is especially well suited for endoscopically quantifying the cartilage tissue, for example in joints, and for endoscopically quantifying the epithelial structures of hollow organs.
It is further preferred in this connection if the ultrasound generation means comprise at least one piezoelectric ultrasonographic transducer and the light applicator means comprise at least one light pipe ending substantially centrally in a radiation surface of the ultrasonic transducer.
Implementing the system with an endoscopic applicator provides the advantage that only one applicator system must be used and no additional deflection systems are required for injecting the ultrasonic beam and the light beam into the tissue along the same beam axis.
According to a further preferred embodiment, the light application means and the ultrasound application means comprise a mirror arrangement that is permeable to ultrasound and reflecting to light, or vice versa, in order to inject the ultrasonic pulse and the measuring light beam along the common beam axis.
This feature provides the advantage that existing applicators, namely on the one hand a separate ultrasound applicator and on the other hand a separate light applicator, can be used, the ultrasonic beam and the light beam being then superimposed by means of the mirror arrangement so that both beams can be injected into the tissue along the same beam axis.
According to a further preferred embodiment the beam splitter means and the means for interferometrically superimposing the back-scattered measuring light beam and the reference light beam comprise a single-beam or multiple-beam interferometer, preferably a Michelson interferometer.
The use of a single-beam or a multiple-beam interferometer, preferably a Michelson interferometer, has proven its value in optical coherence tomography and can be implemented equally in the system according to the invention, at especially low cost, for example as part of an optical driving and evaluation unit.
Further advantages are evident from the description below and the appended drawings.
It is understood that the features recited above and those yet to be explained below can be used not only in the respective combination indicated, but also in other combinations or in isolation, without leaving the context of the present invention.